Since the discovery of hepatitis B surface antigen (HBsAg) by Blumberg, Bull. N.Y. Acad. Med. 1964, 40, 7 and of hepatitis A virus (HAV) Feinstone et al., Science, 73, 182, 1026, hepatitis types A and B have become distinguishable by specific serological tests. A further type of hepatitis, in which no agent has yet been identified, has been designated "non-A, non-B (NANB) hepatitis". In the United States of America, where HBsAg-positive donor blood now is excluded from use in transfusions, non-A, non-B hepatitis accounts for approximately 89% of cases of post-transfusion hepatitis, Alter et al., Lancet 2:838-841, 1975, Alter et al., Am. J. Med. Sci., 270:329-334, 1975. Between 5.4 and 18.5% of Americans receiving five units or less of transfused blood develop non-A, non-B hepatitis, Alter et al., op. cit. Although the name "hepatitis C" has been proposed for this disease, most clinicians and investigators have continued to refer to it as non-A, non-B hepatitis because circumstantial evidence suggests that more than one agent may transmit this disease. The diagnosis of non-A, non-B hepatitis is still based on the exclusion by serologic tests of known etiologic agents: HAV and hepatitis B virus (HBV), cytomegalovirus, Epstein-Barr virus, varicella-zoster, or herpes simplex and of Toxic and drug related hepatitis.
In spite of all efforts, the etiologic agent(s) of non-A, non-B hepatitis is still unknown and there is no serologic test available for diagnosis of the disease or identification of chronic carriers.
A variety of particles supposedly associated with non-A, non-B hepatitis have been found in the serum of humans or chimpanzees, having widely different morphology, and ranging in size from 20-27 nm (Gibo et al., 1980; 25-30 nm (Bradley et al., 1979; Yoshisawa et al., 1980; Mori et al., 1980); 36.5 and 61 nm (Diermietzel et al., 1980); 35-40 nm (Hantz et al., 1980) to 60-80 nm (Prince et al., 1978). In 1979 Coursaget et al., described 60 nm particles resembling toga-virus, found in urine and some times in serum of non-A, non-B hepatitis. None of these particles have been shown to be consistently associated with the illness; therefore, it has been concluded that the specific agent of non-A, non-B hepatitis has not yet been discovered.
Similarly various antigen-antibody systems supposedly associated with non-A, non-B hepatitis have been reported in the literature. The first non-A, non-B antigen-antibody precipitin reaction was purportedly found by Schirachi et al., in 1978. However, this was shown to be non-specific (Suh et al., 1982), as were antigen-antibody systems for non-A, non-B hepatitis, detected later such as those reported by Tabor et al., (1979); Vitvitski et al., (1979); Overby et al., (1980); Renger et al., (1980); Arnold et al., (1980); Prince et al., (1980); Trepo et al., (1980); Alberti et al., (1980). The specificity of any of these antigen-antibody reactions for non-A, non-B hepatitis has has not been demonstrated and most of them have been shown to detect non-specific immune complexes rather than specific viral components (Suh et al., 1981; Hoofnagle, 1981) or abnormal lipoproteins produced as a result of acute liver damage in non-A, non-B and other forms of viral hepatitis (Hui et al., 1983).
Immune complexes have been demonstrated in cases of non-A, non-B hepatitis by Dienstag et al. (1979); Storch and Hagert (1980) and Pennert et al. (1980), but no specific non-A, non-B antigenic component could be identified. More recently, Poralla et al. (1983) failed to identify the antigen described as non-A, non-B specific by Arnold (1980) in circulating immune complexes in the serum of non-A, non-B hepatitis patients. Also, rheumatoid factor-like reactions may interfere in assays designed to detect non-A, non-B hepatitis antigens, leading to false positive results (Roggendorf and Deinhardt, 1983; Duermeyer, 1984).
This subject has been reviewed by R. J. Gerety (Non-A, Non-B Hepatitis, Academic Press, 1981, Chapter 13, pp 207-228), who concludes that neither viral particles nor antigens specific for non-A, non-B hepatitis have yet been positively identified.
In summary, it is apparent that no specific relationship to non-A, non-B hepatitis infection can be claimed for the diverse particles and antigens found up until now. The agent, or agents which causes non-A, non-B hepatitis remains, until now, unknown; and, until now, there has been no discovery of a true and specific antigen for non-A, non-B hepatitis.